16-week Comparative Effectiveness Trial of Lamotrigine vs. Fluoxetine for Bipolar Depression

NCT02389712 | Terminated Phase 4 Results DMC

• 2 other identifiers: 13-003545-1UL1TR000135
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The FLAME Study is a 16-week clinical trial to study treatment with lamotrigine or fluoxetine in bipolar I, II and bipolar schizoaffective depressed adults. The purpose of the trial is to have a better understanding of whether individuals with a particular gene type and other inherited biological markers will have a good response to fluoxetine or lamotrigine, or alternatively, would be more likely to have side effects to this medication.

Conditions

Bipolar Disorder

Keywords

Bipolar Disorder; Mayo Clinic

Outcome Measures

Primary Outcomes (1)

• Inventory for Depressive Symptoms

  12 weeks

Study Arms (2)

Lamotrigine

ACTIVE COMPARATOR

Subjects on this arm will be randomized to Lamotrigine.

Drug: Lamotrigine

Fluoxetine

ACTIVE COMPARATOR

Subjects on this arm will be randomized to Fluoxetine.

Drug: Fluoxetine

Interventions

Lamotrigine DRUG

Lamotrigine dosing: 25 mg daily x 2 weeks, 50 mg daily x 2 weeks, 100 mg daily x 2 weeks, 200 mg (100 mg bid)) x 4 weeks. If patient still has at least mild depressive symptoms, the dose can be increased to 300 mg daily for 2 weeks and 400 mg for 4 weeks. Dose will be held for treatment response and can be reduced for side effects.

Also known as: Lamictal

Lamotrigine

Fluoxetine DRUG

Fluoxetine dosing: 20mg for month 1, 40mg for month 2, and if still depressed (CGI ≥ 3) 60mg for month 3 and 4. Lower doses of fluoxetine will be prescribed for those with side effects. For known Cytochrome P450 2D6 poor metabolizers, fluoxetine will not be dosed \> 40mg.

Also known as: Prozac

Fluoxetine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult participants, age 18-65.
• Outpatients or inpatients with a diagnosis of bipolar I, II or schizoaffective bipolar disorder, depressed phase, non-psychotic, (DSM-5 criteria, Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders Module D confirmed)
• At least mild symptom severity of depression as defined by the Clinical Global Impression for Bipolar Disorder (CGI-BP, Spearing et al. 1997) \>2.
• Bipolar I participants must be on conventional mood stabilizing treatment \[lithium, divalproex or valproate, or an atypical antipsychotic\]. Participants with a bipolar II disorder may pursue the FLAME Study as monotherapy.
• Negative urine pregnancy test.
• Participants not planning pregnancy in the near future (6 months).
• Negative urine toxicology screen (except cannabis).
• No evidence of clinically significant laboratory screening tests (complete blood count (CBC); electrolytes; thyroid stimulating hormone (TSH); creatinine/blood urea nitrogen, Aspartate Aminotransferase (AST)/ALT). Clinical laboratory evaluation within the last three months is acceptable.

You may not qualify if:

• Inability or unwilling to provide informed consent.
• Inability to understand English.
• Actively suicidal participants at screening or enrollment visit as defined by a response of 3 or 4 on question 4 of the Bipolar Inventory of Symptoms Scale (BISS).
• Active delusions or hallucinations defined as a score of 3 or 4 on the BISS question 40 (persecutory ideas) or 41 (delusions or hallucinations).
• Impaired insight as defined as a score of 3 or 4 on BISS question 42 (insight).
• Hypomania defined by a BISS manic subscore of ≥15.
• Axis I or II comorbidity that by referring mental health professional and/or study psychiatrist is primary need of treatment. (This will be assessed by the site principal investigator, who has \>10 years clinical experience with this population. Hospital discharge summaries and outpatient medical records may be reviewed (i.e., adequate trials of mood stabilizing treatments with minimal to no response, prominent self-injurious behavior in the absence of significant mood symptomatology, or atypical cycle patterns) to make this decision.
• Pregnant participants
• Unwilling or unable to taper any current antidepressant therapy
• Participants currently breastfeeding
• Female not practicing a reliable form of birth control (condom, intrauterine device (IUD), Depo-Provera injection)
• Due to lamotrigine pharmacokinetics, female subjects wishing to commence oral contraceptive therapy (OCT) within 3 months of enrollment date or anticipate discontinuing OCT during study (stable oral contraceptive therapy exception).
• History of active substance abuse disorder within the last 3 months (other than caffeine or cannabis)
• Participants with medical contraindications that preclude lamotrigine or fluoxetine treatment
• History of severe adverse reaction to lamotrigine and/or fluoxetine

Sponsors & Collaborators

• Mayo Clinic: lead
• J Willard and Alice S. Marriott Foundation: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Lamotrigine; Fluoxetine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Propylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Mark A. Frye, M.D.
• Organization: Mayo Clinic

MFrye@mayo.edu

507-255-7164

Study Officials

• Mark A Frye, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: March 10, 2015
• First Posted: March 17, 2015
• Study Start: March 1, 2015
• Primary Completion: May 23, 2018
• Study Completion: May 23, 2018
• Last Updated: June 19, 2019
• Results First Posted: June 11, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)